In the past, iontophoresis has been defined as the introduction, by means of electric current, of ions of soluble salts into the tissues of the body for therapeutic purposes. Iontophoretic devices for delivering ionized drugs through the skin have been known since the early 1900's. Deutsche UK Pat. No. 410,009 (1934) describes an iontophoretic device which overcame one of the disadvantages of such earlier devices, namely that the patient was required to be immobilized near the source of the electric current. The Deutsche device was powered by a galvanic cell formed from the electrodes and the material containing the drug to be delivered. The galvanic cell produced the current necessary for iontophoretic delivery of the drug. Thus, this device permitted the patient freedom of movement during iontophoretic drug delivery.
Today, iontophoretic drug delivery is not limited to delivery of ions into the body via electrical current. For example, iontophoretic devices can deliver an uncharged drug into the body via electroosmosis. Electroosmosis is defined as the transdermal flux of a liquid solvent containing an uncharged drug or agent induced by an electric field. Thus, the terms "iontophoretic" and "electrotransport", as used herein, include, but are not limited to, (1) the delivery of charged drugs or agents by electromigration, (2) the delivery of uncharged drugs or agents by the process of electroosmosis, (3) the delivery of charged drugs or agents by the combined processes of electromigration and electroosmosis, (4) the delivery of a mixture of charged and uncharged drugs or agents by the combined processes of electromigration and electroosmosis, and (5) the delivery of agents through pathways created in situ by electroporation. Therefore, a general definition of "iontophoresis" or "electrotransport", as used herein, is the transport of a substance induced or enhanced by the application of an electric potential.
A number of U.S. patents have issued in the iontophoretic agent delivery field. For example, Vernon et al, U.S. Pat. No. 3,991,755; Jacobsen et al, U.S. Pat. No. 4,141,359; Wilson, U.S. Pat. No. 4,398,545; and Jacobsen, U.S. Pat. No. 4,250,878 disclose examples of iontophoretic devices and applications thereof. The iontophoresis process has been useful in the transdermal administration of medications or drugs including lidocaine hydrochloride, hydrocortisone, fluoride, penicillin, dexamethasone sodium phosphate, and insulin, among others. Perhaps the most common use of iontophoresis is in diagnosing cystic fibrosis by delivering pilocarpine salts iontophoretically. The pilocarpine stimulates sweat production; the sweat is collected and analyzed for its chlorine content to detect the presence of the disease.
In presently known iontophoretic devices, at least two electrodes are required. Both electrodes are located in intimate electrical contact with some portion of the skin, nails, or other membrane surface of the body, such that chemical species transport through a body surface is accomplished. One electrode, called the active or donor electrode, is the electrode from which the ionic agent, medication, drug or drug precursor is delivered into the body. The other electrode, termed the counter or return electrode, serves to close the electrical circuit through the body. For example, if the ionic agent to be delivered is positively charged, i.e. a cation, then the anode will be the active or donor electrode, while the cathode serves to complete the circuit. Alternatively, if the ionic agent is negatively charged, i.e. an anion, the cathode will be the donor electrode. Additionally, both the anode and cathode may be used to deliver drugs if both anionic and cationic drug ions are to be delivered. Thus, a complete electrical circuit is formed from electrical contact of the power source to the donor electrode, the donor electrode to the body, the body to the counter electrode, and the counter electrode to the power source.
Iontophoretic delivery devices generally require a reservoir or source of the beneficial agent to be delivered to the body. Examples of such agent reservoirs include a pouch or cavity as described in the previously mentioned Jacobsen patent, U.S. Pat. No. 4,250,878, a porous sponge or pad as disclosed in Jacobsen et al patent, U.S. Pat. No. 4,141,359, and a preformed gel body as described in the Webster patent, U.S. Pat. No. 4,383,529, and the Ariura et al patent, U.S. Pat. No. 4,474,570. Such drug reservoirs are electrically connected to the anode or the cathode of an iontophoretic device to provide a fixed or renewable source of one or more desired agents.
Typically, self-contained iontophoretic delivery devices are designed for contact with only one body surface, such as with electrotransport devices which are placed on the surface of a patient's skin. Structurally, the counter and donor electrodes are usually positioned side by side separated by an insulator, both electrodes being in ion transmitting relation with the same body surface on the same face of the device. This type of electrotransport device is not ideally suited to an environment exposed to body fluids, because of possible short circuiting between the electrodes and/or agent reservoirs via the body fluid. Exemplary of such environments are the oral, nasal, vaginal, ocular and anal cavities. If short-circuiting occurs in such an environment, the iontophoretic agent delivery device merely delivers the agent into the body fluid, e.g. the saliva, and not through the body surface, e.g. buccal membrane, for transport into the blood stream.
Another major issue in iontophoretic delivery systems is the power source. Typically, the power source represents a significant portion of the system cost. In addition, in self-contained systems, the power source is usually formed from one or more batteries having limited useful lives. Thus, a continuing goal in the design of iontophoretic delivery systems is the reduction of power requirements, for example, by reducing the resistance to current flow. Since the major electrical resistance is represented by the two layers of skin through which current typically flows in prior art systems, a reduction in this resistance, resulting in a corresponding reduction in power requirements, would be highly desirable.
Thus, there is a need for device for iontophoretic agent delivery through a mucosal membrane which minimizes the probability of short-circuiting when exposed to body fluids. In addition, there is a further need for a device suitably shaped for iontophoretic agent delivery through two opposing body surfaces. A further need exists for reduction of the cross-sectional area required for an iontophoretic system at a desired agent delivery rate and for reduction of the power requirements for an iontophoretic agent delivery system.